Pistachio (Pistacia vera L.), cultivated in arid and semi-arid regions, is one of the most important nuts worldwide. However, the mechanisms underlying salinity tolerance of this plant is not well understood. Studies were carried out both at physiological and molecular level to unravel the metabolic pathways associated with the salt tolerance mechanisms in various cultivars. Five one-year-old pistachio rootstocks were treated with four saline water regimes for 100 days. Salinity decreased total chlorophyll content and carotenoids in the leaves, and ascorbic acid and total soluble proteins in both leaves and roots. Total phenolic compounds, proline, glycine betaine, and H2O2 content increased in all rootstocks. Three different ion exclusion strategies were observed in rootstocks, (i) Na+ exclusion in UCB-1, (ii) Cl- exclusion in Badami, (iii) and similar concentrations of Na+ and Cl- in the leaves and roots of Ghazvini, Akbari and Kale-Ghouchi. Rootstock UCB-1 exhibited better intonate to the salinity stress followed by Badami, Ghazvini, KG, and Akbari. Two contrasting rootstocks to salinity stress UCB-1 and Akbari were used for further comparative proteome studies. Total proteins were isolated from the roots treated with different NaCl concentrations. The proteins were characterized using high throughput LC MS/MS spectrometry searched against Citrus database. Over 1600 protein IDs were detected among which, the comparative analysis revealed 153 more abundant and 69 low abundant proteins in UCB-1 and 340 more abundant and 18 low abundant proteins in Akbari. The majority of identified proteins have the functions related to stress responsive proteins, signal transduction, cell wall and cytoskeleton metabolism, and transcription factor. The data suggests a strong linkage of molecular mechanism with the physiological traits in the cultivars with various salt tolerances, and confirmed with enzyme assays and transcript analysis. The results lead to further functional elucidation and genetic engineering.